Molecular genetic evidence points to the retinoblastoma susceptibility gene (RB1) as important in tumorigenesis of retinoblastoma, osteosarcoma, breast cancer, soft tissue sarcoma, lung cancer, bladder cancer, and glioblastoma. Many of these cancers which have been shown to lose the expression of the RB1 gene, have been shown to segregate in families, either as single cancers or as part of a cluster of cancers cosegregating in a family. One possibility is that mutations of one allele of the RB1 gene result in predisposition to these cancers in those family members that inherit the mutation. It is possible that by analyzing mutations in the RB1 gene in tumor tissue from familial and sporadic forms of these different tumors and from constitutional tissues in affected family members, it may be possible to identify regions of the gene important in specifying tissue susceptibility and disease phenotype. It may also provide insight into the role of the RB1 gene in predisposition and tumorigenesis.